a study evaluating safety and efficacy of c-car039 treatment in nhl subjects

Conditions: Non-Hodgkin's B-cell Lymphoma

Summary: the trial is a single arm, single-center, non-randomized phase i clinical trial which is designed to evaluate the safety and efficacy of c-car039 in treatment of relapsed or refractory nhl patients

this study plans to enroll 25 patients to assess the safety and efficacy of c-car039. subjects who meet the eligibility criteria will receive a single dose of c-car039 injection. the study will include the following sequential phases: screening, apheresis and c-car039 manufacturing, bridging (if needed), baseline, lymphodepletion, c-car039 infusion, and follow-up visit.

Eligibility criteria:
inclusion criteria: * 1. volunteered to participate in this study and signed informed consent * 2. age 18-75 years old, male or female * 3. cd19 or cd20 positive dlbcl (including pmbcl and tfl), fl and mcl confirmed by cytology or histology according to who2016 criteria. for cd20-positive subjects, they should have received at least one regimen containing anti-cd20-targeted therapy (such as rituximab). if they do not complete the regimen due to intolerance, the cause should be recorded. * 4. relapsed or refractory disease after ≥ 2 lines (for fl, at least 3 lines) of standard therapy or relapsed after autologous stem cell transplantation (asct) * 5. at least one measurable lesion (ldi ≥ 1.5 cm); * 6. at least two weeks from last treatment (radiation, chemotherapy, mab, etc) to apheresis; * 7. lvef≥ 50% (echo) * 8. no active pulmonary infections, normal or mild impaired pulmonary function and spo2≥92% * 9. laboratory criteria: anc≥1.0×109/l; platelets≥50×109/l; serum total bilirubin ≤1.5x uln; creatinine≤ uln; ast and alt≤3x uln * 10. no contraindications of apheresis; * 11. expected survival ≥ 3months * 12. ecog score 0 or 1 exclusion criteria: * 1. have a history of allergy to cellular products; * 2. according to the nyha cardiac function grading standards, patients with grade iii or iv cardiac dysfunction; * 3. a history of craniocerebral trauma, disturbance of consciousness, epilepsy, cerebrovascular ischemia, cerebrovascular hemorrhagic disease, etc.; * 4. patients with central nervous system involvement; * 5. patients with autoimmune diseases, immunodeficiency or other conditions requiring immunosuppressive therapy; * 6. received allogeneic hematopoietic stem cell transplantation before; * 7. previous use of any car t cell product or other genetically modified t cell therapy; * 8. autologous stem cell transplantation within 6 weeks before infusion; * 9. severe active infections (except for simple urinary tract infections, bacterial pharyngitis), or currently undergoing intravenous infusion of antibiotics. however, prophylactic antibiotic, antiviral and antifungal infection treatments are permissible; * 10. live vaccination within 4 weeks prior to apheresis; * 11. people infected with hiv, hbv, hcv and tppa/rpr, and carriers with hbv; * 12. a history of alcohol abuse, drug use or mental illness; * 13. subjects who are not sterilized and have any of the following conditions: 1. are pregnant/lactating; or 2. planned pregnancy during the trial; or 3. being fertile and unable to use effective contraception; * 14. severe hypersensitivity to fludarabine or cyclophosphamide; * 15. a history of other primary cancers other than the following: 1. non-melanoma tumors such as basal cell carcinoma of the skin that are cured by excision 2. cured in situ cancers such as cervical, bladder, or breast cancer * 16. the investigators consider that the subject has other conditions that are not suitable for this trial.